Neointimal hyperplasia is one of the major obstacles limiting the long-term clinical efficiency of cardiovascular intervention including angioplasty, bypass, and transplantation arteriopathy, etc., (Degertekin, et al., Circulation., 106:1610-1613 (2002)). Neointima formation also contributes to the development and progression of several proliferative cardiovascular diseases such as atherosclerosis, hypertension, and diabetic vascular complications (Frank, et al., Curr. Opin. Lipidol., 15:523 (2004)). Under pathological conditions, vascular injury causes denudation of endothelial layer, which triggers a series of acute and chronic inflammatory responses characterized by the production of various different growth factors or inflammatory cytokines (Murakami, et al., Am J Physiol Lung Cell Mol Physiol., 272:L197-L202 (1997); Cotran, et al., J Am Soc Nephrol., 1:225-235 (1990)). Media layer smooth muscle cell (SMC) proliferation and migration in response to the injury-induced factors (such as platelet-derived growth factor, or PDGF) are essential events contributing to subsequent neointimal thickening (Fingerle, et al., Proc Natl Acad Sci., 86:8412 (1989); Clowes, et a., Circ. Res., 56:139-145 (1985)) which eventually leads to vessel narrowing. Re-endothelialization halts neointima formation and initiates the successful vascular repair (Bauters, et al., Prog. Cardiovasc. Dis., 40:107-116 (1997); Kinlay, et al., Curr. Opin. Lipidol., 12:383 (2001)). However, currently available anti-neointimal drugs indiscriminately block the proliferation of both SMCs and endothelial cells (EC), leading to impaired re-endothelialization and prolonged wound healing process. There remains a need to develop an anti-proliferation strategy that is SMC-sensitive.
Therefore, it is an object of the invention to provide compositions, devices, grafts, and methods of use thereof for reducing or preventing smooth muscle cell proliferation in a subject.
It is a further object of the invention to provide compositions, devices, grafts, and methods of use thereof for promoting or enhancing re-endothelialization in a subject.
It is also an object of the invention to provide compositions, methods, and devices for reducing or preventing neointima formation, restenosis, or a combination thereof in a subject.